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Dropping resveratrol


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#61 Anthony_Loera

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Posted 19 February 2008 - 07:17 PM

Hmm...

thats our old wholesale list, at around the time of the Vegas NPA show last year.

A

Hi... what price are you looking for that would start making it acceptable again for a one income family?

Just curious.
A



The profit margin seems to be around 50%. The profit margin is even higher if revgenetics has a profit on their wholesale products. Seems to me like a very good business.

Download for wholesale prices >



#62 missminni

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Posted 19 February 2008 - 07:23 PM

Which begs the question. Has Sirtis released the lean mice data YET?

On condition of anonymity a highly placed officer of SIRTRIS Corporation revealed why it is taking so long for the clinical trials data to be published. "We didn't expect the laxative effects to be so strong" he said, " we are spending a lot of money, time and effort in cleaning the facility".

DO you have a link?

we are spending a lot of money, time and effort in cleaning the facility".


What the heck does that mean? That they didn't follow FDA-GMP guidlines? A simple answer would be is they need a better formulation (use less product = less side effects) or use a more potent molecule.

And why can't they publish data because of a laxative effect?

The part about cleaning the facility might be a joke, but I wonder about the strong laxative side effects, since
mine have only gotten worse.


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#63 Anthony_Loera

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Posted 19 February 2008 - 07:28 PM

Mike,

I presume you would buy powder, and not care about capsules correct?
(it appears your dosage suggests you prepare it)

Funny, last years biggest request was about getting 99% rsv at around $100 a bottle,
this year it has to be micronized rsv at $167 for every 100grams?

Hehe... We got close with last years request (we got a 99% bottle down to $103 at one point in time last year)
Maybe we can help you out with this years request...

A



$30 dollars a month per person in your family isn't unreasonable ...providing it was high quality, micronized 99% purity Resveratrol at a 1.5g per day doseage. That would be $0.67 a gram ....... the closest we have that doesn't involved a multi-kilogram purchase from Revgenetics for thousands of dollars is Vitalprime, as as far as I am concerned, its still suspect. So our current best bet is Mega-Resveratrol at the 240g mark at 1.80 a gram ...or nearly triple to what I would see as a reasonable price point for most families, especially when you multiply that by 2 or more to account for other family members. Until it comes down, it will be out of range of the average american family.



To me .....I would pay $75 each for myself and my wife ($150.00 total) for high quality, micronized 99% purity Resveratrol at a 1.5g per day doseage. That would be $1.67 / gram price point for me. Still out of range of the revgenetics product at an afforable quantity (though if I could afford to drop cash for 25 kilos, I could get it at 33% the price of the 100 gram product ...but who has 16k to throw at resv).



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#64 mikeinnaples

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Posted 19 February 2008 - 08:23 PM

Well to be honest, due to your presence on the boards and what seems to be genuine concern for the consumer and having a quality product, all of my future business will be with you even with the slightly higher price point. Having trust in a product does more in gaining my loyalty than price. Unless the price is unreasonable that is :~

#65 maxwatt

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Posted 19 February 2008 - 08:36 PM

....
The part about cleaning the facility might be a joke, but I wonder about the strong laxative side effects, since
mine have only gotten worse.


Mine have gotten better. I hired a cleaning lady.

Seriously: I take two grams morning and again at night. Sometimes with lecithin, sometimes in milk (or a chocolate egg cream -- milk, seltzer, resveratrol and Fox's U-Bet chocolate syrup). Usually little or no laxative effect, but sometimes it builds up. It may be influenced by other things in the diet. Skipping one or two doses gets things back to normal. The various things I've tried to mitigate the effect are only partly effective. (These were HMB for the butyrate, Inawe did not report good effects with another butyrate compound- Calcium butyrate - so I've not pursued that, a Chinese Herb, Bai Zhi, and Kaopectate, i.e. bismuth subsalicylate).

If I take more than two grams at a time twice a day, or three grams once a day, I will have the problem. This amount seems to be specific to individuals. For my wife, more than 250 mg once a day seems to be the tipping point. Missminni, your tipping point seems to be somewhat under 1 gram twice a day. Another person found it to be 500 mg. Some people take 5 or more grams regularly, no problem. I can't. Is a longer life worth it, if it has to be spent on the toilet? Once a day dosing, at night, with an individually determine maximum tolerated dose may be the best course.

It is possible to use other sirtuin activators. The more potent that I know are silymarin (best bound with phosphatidyl choline (lecithin) as in the product Siliphos ®,) and diadzein, which is not readily available without other soy isoflavones. Unfortunately, silymarin is known to be a laxative for some people. Diadzein was available a dozen years ago, for weightlifters and body builders, but they decided with little direct evidence that it was estrogenic. Yet some people did claim a muscle-building effect.
The people who market Siliphos Silymarin claim a 10 fold increase in serum levels over powder-in-a-capsule. If this delivery system works for resveratrol, one won't need such large doses. Since Silymarin is readily available as a supplement, it may be worth trying to see if it is tolerable. Beyond-a-century sells an 80% extract as powder, and 80% capsules are available from a number of sources. My estimates are that one needs twice the dose of 80% Silymarin to achieve the same sirtuin-activating effect as with resveratrol. The blood levels of resveratrol bound to lecithin, should be something Hedgehog could measure, or perhaps Anthony could have done.

The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed. The Caco cells are also those that passively pass resveratrol into the blood, or conjugate it with a sugar or a sulfur-containing molecule. (Anyone with more specific knowledge please add to this.) People differ genetically in their enzyme levels for these processes. Perhaps the diarrhea indicates one is absorbing an effective dose, or perhaps it indicates the opposite, that one can't absorb enough to be effective. I don't know.

I plan to continue resveratrol for my own use, and I think most people would benefit if they could. Over the past year I've had remarkably positive effects for my osteoarthritis, my average fasting glucose levels seem to have declined by about 20 mg/dl. If the Cardiotrack were more accurate for measuring lipids I could report that too, but it will have to wait for my physical in the next few months. The first two parameters are consistent with a CR mimetic effect. Even if they weren't, the pain relief and increased mobility are worth it for me.

#66 missminni

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Posted 19 February 2008 - 08:52 PM

I haven't given up. I tried Maalox. It helps, and I do have to
keep my dose under a gram at a time.


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#67 inawe

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Posted 19 February 2008 - 09:47 PM

....
The part about cleaning the facility might be a joke, but I wonder about the strong laxative side effects, since
mine have only gotten worse.


Mine have gotten better. I hired a cleaning lady.

Seriously: I take two grams morning and again at night. Sometimes with lecithin, sometimes in milk (or a chocolate egg cream -- milk, seltzer, resveratrol and Fox's U-Bet chocolate syrup). Usually little or no laxative effect, but sometimes it builds up. It may be influenced by other things in the diet. Skipping one or two doses gets things back to normal. The various things I've tried to mitigate the effect are only partly effective. (These were HMB for the butyrate, Inawe did not report good effects with another butyrate compound- Calcium butyrate - so I've not pursued that, a Chinese Herb, Bai Zhi, and Kaopectate, i.e. bismuth subsalicylate).

If I take more than two grams at a time twice a day, or three grams once a day, I will have the problem. This amount seems to be specific to individuals. For my wife, more than 250 mg once a day seems to be the tipping point. Missminni, your tipping point seems to be somewhat under 1 gram twice a day. Another person found it to be 500 mg. Some people take 5 or more grams regularly, no problem. I can't. Is a longer life worth it, if it has to be spent on the toilet? Once a day dosing, at night, with an individually determine maximum tolerated dose may be the best course.

It is possible to use other sirtuin activators. The more potent that I know are silymarin (best bound with phosphatidyl choline (lecithin) as in the product Siliphos ®,) and diadzein, which is not readily available without other soy isoflavones. Unfortunately, silymarin is known to be a laxative for some people. Diadzein was available a dozen years ago, for weightlifters and body builders, but they decided with little direct evidence that it was estrogenic. Yet some people did claim a muscle-building effect.
The people who market Siliphos Silymarin claim a 10 fold increase in serum levels over powder-in-a-capsule. If this delivery system works for resveratrol, one won't need such large doses. Since Silymarin is readily available as a supplement, it may be worth trying to see if it is tolerable. Beyond-a-century sells an 80% extract as powder, and 80% capsules are available from a number of sources. My estimates are that one needs twice the dose of 80% Silymarin to achieve the same sirtuin-activating effect as with resveratrol. The blood levels of resveratrol bound to lecithin, should be something Hedgehog could measure, or perhaps Anthony could have done.

The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed. The Caco cells are also those that passively pass resveratrol into the blood, or conjugate it with a sugar or a sulfur-containing molecule. (Anyone with more specific knowledge please add to this.) People differ genetically in their enzyme levels for these processes. Perhaps the diarrhea indicates one is absorbing an effective dose, or perhaps it indicates the opposite, that one can't absorb enough to be effective. I don't know.

I plan to continue resveratrol for my own use, and I think most people would benefit if they could. Over the past year I've had remarkably positive effects for my osteoarthritis, my average fasting glucose levels seem to have declined by about 20 mg/dl. If the Cardiotrack were more accurate for measuring lipids I could report that too, but it will have to wait for my physical in the next few months. The first two parameters are consistent with a CR mimetic effect. Even if they weren't, the pain relief and increased mobility are worth it for me.

As somebody said (Shakespeare?), metabolism starts in the gut of the beholder. Somebody else said the laxative effect of RSV was a joke. If that's so, you can laugh your butt off.
Once I saw it was a real effect (thanks Pubmed), and not just in my gut, I searched for ways to control it and I think I found it. I take 2 things.
1) From BODYBIO, BUTYRATE. Calcium/Magnesium Butyrate complex, 600 mg, up to 6 capsules/day.
2) Mai Ya. I buy it from www.maxnature.com. I put it in my morning green tea.
Some days you might need more, others less. Just go with the flow.

#68 mikeinnaples

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Posted 19 February 2008 - 09:52 PM

The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed.




I wonder if one were to hammer a ton of resitant starches in their meals every day, if it would up butyrate levels enough without needing a prescription. Make potatoes, bananas, and beans food of choice again .......well cold anyways.

#69 missminni

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Posted 19 February 2008 - 10:12 PM

The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed.




I wonder if one were to hammer a ton of resitant starches in their meals every day, if it would up butyrate levels enough without needing a prescription. Make potatoes, bananas, and beans food of choice again .......well cold anyways.

I agree with the bananas, potatoes and such foods, but NO beans...uh uh. I can't even imagine what that combo would do.

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#70 niner

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Posted 20 February 2008 - 07:33 AM

The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed. The Caco cells are also those that passively pass resveratrol into the blood, or conjugate it with a sugar or a sulfur-containing molecule. (Anyone with more specific knowledge please add to this.) People differ genetically in their enzyme levels for these processes. Perhaps the diarrhea indicates one is absorbing an effective dose, or perhaps it indicates the opposite, that one can't absorb enough to be effective. I don't know.

I've read (somewhere...) that resveratrol can irritate epithelia. Maybe the diarrhea is nothing more than an irritant effect? Or is there a specific effect where resveratrol is causing chlorate(?) secretion? (Sure it's not chloride?) We should really call them intestinal epithelial cells (or maybe there's another name) rather than Caco, since Caco is a specific cell line derived from a colon carcinoma. It's used as a model of intestinal epithelia because it forms consistent and well behaved monolayers. The gut lining contains enzymes for both glucuronidation and sulfation, as you allude. Not to mention P450s. It's an important site of metabolism, which makes sense since that's the way most xenobiotics get in. It also has both influx and efflux transporters. Resveratrol is absorbed by passive diffusion through the cell wall, but is actively pumped back into the the intestinal lumen by a pump in the MultiDrug Resistance pump family. If the resveratrol happens to be glycosylated, it can hitch a ride on a sodium dependent glucose transporter and get in that way, but that process is not as fast as the diffusion of the aglycone.

#71 niner

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Posted 20 February 2008 - 08:00 AM

That is a good question Anthony, let me go through my story in detail and I'll try to find your answer along the way.

I originally started taking resveratrol when I thought I could get the equivalent Sinclair rat study dosage (with fat rats taking 30mg/kg) by taking 5mg/kg using a scaling factor of 1/6 between humans and rats. That would mean taking 340mg a day for me (150lbs) or $10 a month for 50% extract. Pretty cheap.

However, more data comes along and shows that we don't need 1/6 of the rat dosage, but 6x the amount. This means I need to take 180mg/kg a day or 12.24g per day. At this point I upped my dosage to a mere 800mg a day (jumping to $24 a month) and looked for ways to increase the bioavailabiltiy.
[...]
I guess the answer to your question is, when a high purity resveratrol gets down to $10 a month for an effective dosage I'll probably jump back in.

Health_nutty, I think you might be overestimating the amount of resveratrol you need for decent results. Sirtris is getting blood sugar reductions in humans at 2.5 grams/day, albeit with a good formulation. If you took 2.5 g/d as a target, then you would need 75 g/month. If you really want it for $10/month, then it has to be 13 cents/gram. It sounds like decent quality bulk resveratrol is in the ballpark of 50 cents/gram now, but I've heard numbers like 15 cents a gram for fermentation-produced res. I think that it will be a long time (maybe never) before you can buy resveratrol at the retail level for such prices, but if you were willing to go to something like a buck a day, it might not be too long before something is available, at least if you buy a kilo of powder. It would be nice to be able to get a micronized product, and I don't think that has to add all that much to the price.

#72 maxwatt

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Posted 20 February 2008 - 01:34 PM

The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed. The Caco cells are also those that passively pass resveratrol into the blood, or conjugate it with a sugar or a sulfur-containing molecule. (Anyone with more specific knowledge please add to this.) People differ genetically in their enzyme levels for these processes. Perhaps the diarrhea indicates one is absorbing an effective dose, or perhaps it indicates the opposite, that one can't absorb enough to be effective. I don't know.

I've read (somewhere...) that resveratrol can irritate epithelia. Maybe the diarrhea is nothing more than an irritant effect? Or is there a specific effect where resveratrol is causing chlorate(?) secretion? (Sure it's not chloride?) We should really call them intestinal epithelial cells (or maybe there's another name) rather than Caco, since Caco is a specific cell line derived from a colon carcinoma. It's used as a model of intestinal epithelia because it forms consistent and well behaved monolayers. The gut lining contains enzymes for both glucuronidation and sulfation, as you allude. Not to mention P450s. It's an important site of metabolism, which makes sense since that's the way most xenobiotics get in. It also has both influx and efflux transporters. Resveratrol is absorbed by passive diffusion through the cell wall, but is actively pumped back into the the intestinal lumen by a pump in the MultiDrug Resistance pump family. If the resveratrol happens to be glycosylated, it can hitch a ride on a sodium dependent glucose transporter and get in that way, but that process is not as fast as the diffusion of the aglycone.


Thank you for helping clarify. I've reposted the abstract (credit to Inawe for the find) below; they found the main mechanism of action of resveratrol on intestinal epithelia was "cAMP-induced chloride secretion which can be suppressed by butyrate."

lin Cancer Res. 2005 Aug 1;11(15):5651-6.
The chemopreventive agent resveratrol stimulates cyclic AMP-dependent chloride secretion in vitro.Blumenstein I, Keserü B, Wolter F, Stein J.
Division of Gastroenterology and Clinical Nutrition, 1 Department of Medicine, ZAFES, J.W. Goethe-Universität, Theodor-Stern-Kai 7, Frankfort on the Main, Germany.

Resveratrol and its analogs are promising cancer chemoprevention agents, currently under investigation in clinical trials. However, patients administered other plant polyphenols experienced severe diarrhea, likely due to an increase in intracellular cyclic AMP (cAMP). Resveratrol itself raises intracellular cAMP levels in breast cancer cells in vitro. Its future use as a cancer chemopreventive agent could therefore be compromised by its severe side effects. The aim of the study was (a) to define the influence of resveratrol on intestinal Cl(-) secretion and (b) to elucidate possible intracellular transduction pathways involved. Resveratrol caused a dose- and time-dependent increase in DeltaIsc in T(84) cells. The specificity of resveratrol was confirmed by using piceatannol 100 mumol/L, the hydroxylated resveratrol analog, which did not alter DeltaIsc. A significant elevation of [cAMP](i) by resveratrol was assessed in T(84) cells. In mouse jejunum, resveratrol induced a time- and dose-dependent increase in DeltaIsc as well. In bilateral Cl(-)-free medium, as well as after inhibition of protein kinase A, resveratrol-induced DeltaIsc was reduced significantly. Preincubation of T(84) cells with butyrate 2 mmol/L (24 and 48 hours) significantly inhibited resveratrol as well as forskolin-induced Cl(-) secretion. In summary, the main mechanism of action of resveratrol in intestinal epithelia is cAMP-induced chloride secretion which can be suppressed by butyrate. It can therefore be suggested that in cancer chemoprevention, both agents should be combined to reduce an undesired side effect such as diarrhea and to benefit from the known agonistic effect of both agents on differentiation of colon cancer cells.

PMID: 16061885 [PubMed - indexed for MEDLINE]


Inawe suggested Calcium/Magnesium Butyrate complex, 600 mg, up to 6 capsules/day, from BODYBIO.
He also used an herbal preparation I am investigating.

Edited for grammaire and spellling

Edited by maxwatt, 20 February 2008 - 04:07 PM.


#73 docmaas

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Posted 20 February 2008 - 07:22 PM

Hmm...

thats our old wholesale list, at around the time of the Vegas NPA show last year.

A

Hi... what price are you looking for that would start making it acceptable again for a one income family?

Just curious.
A



The profit margin seems to be around 50%. The profit margin is even higher if revgenetics has a profit on their wholesale products. Seems to me like a very good business.

Download for wholesale prices >



I'm still taking 500mg but the laxative effects have tapered off considerably. could be because I'm traveling right now and taking it as a capsule instead of dissoved in yogurt.

Mike

#74 docmaas

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Posted 20 February 2008 - 07:27 PM

Maybe we could get some paragoric and kill 2 birds with one stone. (alluding to your previous comments on recreational drugs)

....
The part about cleaning the facility might be a joke, but I wonder about the strong laxative side effects, since
mine have only gotten worse.


Mine have gotten better. I hired a cleaning lady.

Seriously: I take two grams morning and again at night. Sometimes with lecithin, sometimes in milk (or a chocolate egg cream -- milk, seltzer, resveratrol and Fox's U-Bet chocolate syrup). Usually little or no laxative effect, but sometimes it builds up. It may be influenced by other things in the diet. Skipping one or two doses gets things back to normal. The various things I've tried to mitigate the effect are only partly effective. (These were HMB for the butyrate, Inawe did not report good effects with another butyrate compound- Calcium butyrate - so I've not pursued that, a Chinese Herb, Bai Zhi, and Kaopectate, i.e. bismuth subsalicylate).

If I take more than two grams at a time twice a day, or three grams once a day, I will have the problem. This amount seems to be specific to individuals. For my wife, more than 250 mg once a day seems to be the tipping point. Missminni, your tipping point seems to be somewhat under 1 gram twice a day. Another person found it to be 500 mg. Some people take 5 or more grams regularly, no problem. I can't. Is a longer life worth it, if it has to be spent on the toilet? Once a day dosing, at night, with an individually determine maximum tolerated dose may be the best course.

It is possible to use other sirtuin activators. The more potent that I know are silymarin (best bound with phosphatidyl choline (lecithin) as in the product Siliphos ®,) and diadzein, which is not readily available without other soy isoflavones. Unfortunately, silymarin is known to be a laxative for some people. Diadzein was available a dozen years ago, for weightlifters and body builders, but they decided with little direct evidence that it was estrogenic. Yet some people did claim a muscle-building effect.
The people who market Siliphos Silymarin claim a 10 fold increase in serum levels over powder-in-a-capsule. If this delivery system works for resveratrol, one won't need such large doses. Since Silymarin is readily available as a supplement, it may be worth trying to see if it is tolerable. Beyond-a-century sells an 80% extract as powder, and 80% capsules are available from a number of sources. My estimates are that one needs twice the dose of 80% Silymarin to achieve the same sirtuin-activating effect as with resveratrol. The blood levels of resveratrol bound to lecithin, should be something Hedgehog could measure, or perhaps Anthony could have done.

The laxative effect is known to be due to the Caco cells in the small intestine secreting too much chlorate, and is known to be mitigated by butyrate, which is available as a prescription medication for a genetic disorder affecting the intestines (inawe posted a link to the abstract. in pubmed.) If one could obtain a prescription, or perhabs a pharmacy abroad, that might be what's needed. The Caco cells are also those that passively pass resveratrol into the blood, or conjugate it with a sugar or a sulfur-containing molecule. (Anyone with more specific knowledge please add to this.) People differ genetically in their enzyme levels for these processes. Perhaps the diarrhea indicates one is absorbing an effective dose, or perhaps it indicates the opposite, that one can't absorb enough to be effective. I don't know.

I plan to continue resveratrol for my own use, and I think most people would benefit if they could. Over the past year I've had remarkably positive effects for my osteoarthritis, my average fasting glucose levels seem to have declined by about 20 mg/dl. If the Cardiotrack were more accurate for measuring lipids I could report that too, but it will have to wait for my physical in the next few months. The first two parameters are consistent with a CR mimetic effect. Even if they weren't, the pain relief and increased mobility are worth it for me.



#75 maxwatt

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Posted 20 February 2008 - 07:34 PM

Maybe we could get some paragoric and kill 2 birds with one stone. (alluding to your previous comments on recreational drugs)

(snip redundant quote)


I have a prescription for Vicoden for pain management, and it is almost as effective as paregoric. Believe me, it's no fun being constipated and having diarrhea at the same time.

#76 malbecman

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Posted 20 February 2008 - 07:43 PM

I'm a little surprised by all these laxative reports. I've taken up to 2.5 grams/day, although my usual dose is more like ~800mg, in a lecithin/water mixture and have never had any laxative effects. I'll count my lucky stars, I guess, but it makes me wonder what is really going on there......

#77 sUper GeNius

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Posted 20 February 2008 - 08:09 PM

I have noticed the laxative effect. Previously taking only 1 g of 98%. No problem there. In fact, at that dose, I also took 200mg of the County Life 50%. because I actually preferred the regularity. For the last few days I have been taking only three grams of 98% in the late evening, and it reminds me of being on a very high fiber diet I was on many years ago. I have my regular visit with the porcelain goddess in early morning. Somewhat loose stool. Then I have another very strong urge to go in mid afternoon.

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#78 inawe

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Posted 20 February 2008 - 10:04 PM

I'm a little surprised by all these laxative reports. I've taken up to 2.5 grams/day, although my usual dose is more like ~800mg, in a lecithin/water mixture and have never had any laxative effects. I'll count my lucky stars, I guess, but it makes me wonder what is really going on there......

You probably haven't noticed any other effect of RSV either. Because when it works, it's according to the following pathway
RSV --> LaxATivia --> Sirt1 --> deacetylation.
Just kidding. It all depends on the guts of the beholder: cAMP, motility, opioid receptors, etc.

#79 Smith

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Posted 21 February 2008 - 09:22 PM

I believe people were selling synthetic versions of naturally occurring compounds in the case of "prohormones". Patrick Arnold did this with things like androstenedione , -diol and others. He wasn't prosecuted for that, probably due to a lack of interest and resources by the FDA. He did go to jail, but that was for making the designer steroid in the Balco scandal. He could probably have beaten that, it wasn't on the list of steroids, but he was offered four months in jail versus millions in legal fees. It could make an interesting court case someday. You'll get away with it until they tell you to stop. Which they may never do.

True, there were hundreds of different synthetic version sof prohormones on the market back in 2004 manufactured by dozens of companies. M1T (Methylated 1-Testosterone) being the most popular. The Methylation process allowed the 1-Testosterone molecules to basically bypass the liver and get into the bloodstream. I can attest to it's effectiveness.. Basically a legal form of steroids.. However, my understanding is all methlyated drugs are hard on the liver, thus many body builders would take M1T with Primrose oil and/or other supplements to help protect the liver; furthermore, one would only take M1T for about 8 weeks maximum, whereas with RESV, its a constant thing, so I suspect Methylated RESV would not be a good idea in the long run.

Acetylated resveratrol would be interesting. Water soluble, gets in the cell, stays there pumping out resveratrol....

Not sure what the difference between Methylated and Acetylated RESV would be, but if the Acetylated RESV did not have liver side-effects, it could be a very effective way of getting RESV to bypass the liver. It can't be very difficult or expensive, as it was almost overnight that the Pro-hormone companies started pumping out Methylated versions of their products and increased bio-availbility by an order of magnitude.

Edited by Smith, 21 February 2008 - 09:23 PM.


#80 ilanso

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Posted 22 February 2008 - 08:00 AM

As somebody said (Shakespeare?), metabolism starts in the gut of the beholder. Somebody else said the laxative effect of RSV was a joke. If that's so, you can laugh your butt off.


It's a matter of formal logic: RSV makes for a longer life --> Life is shitty --> longer life is ...

On a more serious note, I am taking 2 * 3.5g (99%) with no such effects noted (it is dissolved in flax oil and chased with a red wine shot). Both times I add 600 mg 50% RSV, 1g sillymarin, green tea extract (700mg) and ellagin (1g) among several other things. Often, I gulp all this down with a glass of home-made buttermilk. Doesn't it sound just like a frat house hazing recipe? And yet I can now be described as just "regular". That is not to say I didn't have my own share of the runs at some point (walking the dog in the woods kind of became a reciprocating deal). Could be I've developed immunity or have since added some counteracting component.

#81 missminni

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Posted 22 February 2008 - 12:39 PM

As somebody said (Shakespeare?), metabolism starts in the gut of the beholder. Somebody else said the laxative effect of RSV was a joke. If that's so, you can laugh your butt off.


It's a matter of formal logic: RSV makes for a longer life --> Life is shitty --> longer life is ...

On a more serious note, I am taking 2 * 3.5g (99%) with no such effects noted (it is dissolved in flax oil and chased with a red wine shot). Both times I add 600 mg 50% RSV, 1g sillymarin, green tea extract (700mg) and ellagin (1g) among several other things. Often, I gulp all this down with a glass of home-made buttermilk. Doesn't it sound just like a frat house hazing recipe? And yet I can now be described as just "regular". That is not to say I didn't have my own share of the runs at some point (walking the dog in the woods kind of became a reciprocating deal). Could be I've developed immunity or have since added some counteracting component.

I think this is the answer. I recently tried taking it with yogurt and banana and noticed an improvement.
Unfortunately I have to stop all supplements for two weeks due to the most
horrible case of stress related hives, but when I resume I'll try some different combos. Suggestions?


#82 Brainbox

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Posted 22 February 2008 - 03:42 PM

Funny, last years biggest request was about getting 99% rsv at around $100 a bottle,
this year it has to be micronized rsv at $167 for every 100grams?

Hehe... We got close with last years request (we got a 99% bottle down to $103 at one point in time last year)
Maybe we can help you out with this years request...

Nah, still to expensive.... :)


:)

Edited by brainbox, 22 February 2008 - 03:42 PM.


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#83 lynx

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Posted 22 February 2008 - 03:53 PM

I'm convinced I would have to take huge amounts to overcome the bioavailability issue (we require 6x the equivalent rat amount).

No, Human Equivalent Dose = rat divided by 6.2, not multiplied

#84 Brainbox

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Posted 22 February 2008 - 04:02 PM

Unfortunately I have to stop all supplements for two weeks due to the most
horrible case of stress related hives, but when I resume I'll try some different combos. Suggestions?

I experienced a similar issue last year. I think, based on that experience, you would need to evaluate your entire regimen. In my case the culprit where the proteolytic enzymes I was taking at the time.

#85 missminni

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Posted 22 February 2008 - 04:10 PM

Unfortunately I have to stop all supplements for two weeks due to the most
horrible case of stress related hives, but when I resume I'll try some different combos. Suggestions?

I experienced a similar issue last year. I think, based on that experience, you would need to evaluate your entire regimen. In my case the culprit where the proteolytic enzymes I was taking at the time.

Actually I stopped Res for a week prior to my hive breakout, and when I
reintroduced it at doses over a gram, the diarrhea returned. I don't think I am taking any proteolytic enzymes, but
I am not sure. Would yogurt come under that description?


#86 Brainbox

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Posted 22 February 2008 - 04:24 PM

Unfortunately I have to stop all supplements for two weeks due to the most
horrible case of stress related hives, but when I resume I'll try some different combos. Suggestions?

I experienced a similar issue last year. I think, based on that experience, you would need to evaluate your entire regimen. In my case the culprit where the proteolytic enzymes I was taking at the time.

Actually I stopped Res for a week prior to my hive breakout, and when I
reintroduced it at doses over a gram, the diarrhea returned. I don't think I am taking any proteolytic enzymes, but
I am not sure. Would yogurt come under that description?

No. It was a product called Wobenzyme that I was taking. The positive effect of it is questionable anyway. It apparently introduced some form of histamine sensitivity, so that taking other supplements on top of the enzymes created my hives. First it seemed that several supplement were part of the cause, but after dropping the enzymes the issue was entirely gone, also when I took the originally eliminated supps again. I still keep my fingers crossed. :)
In your case, the cause could be something entirely different, and I would evaluate every individual supp you are taking. Unfortunately, my experience doesn't give you a head-start in this...

#87 Hedgehog

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Posted 22 February 2008 - 04:26 PM

Unfortunately I have to stop all supplements for two weeks due to the most
horrible case of stress related hives, but when I resume I'll try some different combos. Suggestions?

I experienced a similar issue last year. I think, based on that experience, you would need to evaluate your entire regimen. In my case the culprit where the proteolytic enzymes I was taking at the time.

Actually I stopped Res for a week prior to my hive breakout, and when I
reintroduced it at doses over a gram, the diarrhea returned. I don't think I am taking any proteolytic enzymes, but
I am not sure. Would yogurt come under that description?


Hi Missiminni,

Have you tried taking smaller doses throughout the day?

Maybe 300mg at breakfest, then again at lunch and then at dinner.

Are you taking resveratrol with a meal or on a empty stomach?

#88 missminni

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Posted 22 February 2008 - 04:52 PM

Unfortunately I have to stop all supplements for two weeks due to the most
horrible case of stress related hives, but when I resume I'll try some different combos. Suggestions?

I experienced a similar issue last year. I think, based on that experience, you would need to evaluate your entire regimen. In my case the culprit where the proteolytic enzymes I was taking at the time.

Actually I stopped Res for a week prior to my hive breakout, and when I
reintroduced it at doses over a gram, the diarrhea returned. I don't think I am taking any proteolytic enzymes, but
I am not sure. Would yogurt come under that description?


Hi Missiminni,

Have you tried taking smaller doses throughout the day?

Maybe 300mg at breakfest, then again at lunch and then at dinner.

Are you taking resveratrol with a meal or on a empty stomach?

At 300 mg I'm fine. It's only when I get up to 1g that I have that problem. I've taken it both with meals
and on an empty stomach. It's definitely better with meals but still I can't go much over 1g throughout the day without getting cramps and diarrhea.
I am thinking that if I take it in a few 300 to 400 mg doses with banana or rice I might be able to tolerate it and get more in my system.
As soon as I can start, I will try.

My hives are not related to the Res or to any supplements I am taking. They started from stress on Jan 28th as two little patches on my cheeks.
It looked like rouge. Last week they seemed to get gradually worse as stress increased, and then early this week I thought they were getting better but co-incidentally, or maybe not
so coincidentally, my face swelled up like a balloon on Wed between 10 and 11PM, the very hour of the lunar eclipse. I am thinking that is what put me over the top. I literally had a moon face. Since the moon affects tides, and we know it affects women's menses, I think it might be the smoking gun here.


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#89 speedlet

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Posted 22 February 2008 - 10:12 PM

Simple question:

Are there any studies that have shown resveratrol to extend life among healthy, non-obese mammals, such as mice?

Obviously, there are the much-publicized studies in which resveratrol allows obese mice to live as long as non-obese mice, but this doesn't have much value unless you're an obese human. And there are the studies with yeast, fruit flies and fish, but at this point there should be some body of research in mammals such as mice, rats, dogs, or monkeys.

Someone, such as Sirtris, has to have done a simple lifespan study with mice by now. There must be some sort of conclusive result.

*****

I ask because Michael Rae, a practitioner of Caloric Restriction and co-author of Aubrey de Grey's book, contends that Resveratrol does not extend life beyond the normal lifespan in healthy mice and may in fact be carcinogenic.

It seems there is a political faultline between the de Grey/Methuselah camp and the Sirtris/Resveratrol camp, as if each seems to think that the other is competing for funding, credibility or support.

But Rae does ask a simple question -- "show me the 45-month-old mouse" -- that should be fairly easy to answer.

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#90 niner

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Posted 22 February 2008 - 10:47 PM

Simple question:

Are there any studies that have shown resveratrol to extend life among healthy, non-obese mammals, such as mice?

Obviously, there are the much-publicized studies in which resveratrol allows obese mice to live as long as non-obese mice, but this doesn't have much value unless you're an obese human. And there are the studies with yeast, fruit flies and fish, but at this point there should be some body of research in mammals such as mice, rats, dogs, or monkeys.

Someone, such as Sirtris, has to have done a simple lifespan study with mice by now. There must be some sort of conclusive result.

*****

I ask because Michael Rae, a practitioner of Caloric Restriction and co-author of Aubrey de Grey's book, contends that Resveratrol does not extend life beyond the normal lifespan in healthy mice and may in fact be carcinogenic.

It seems there is a political faultline between the de Grey/Methuselah camp and the Sirtris/Resveratrol camp, as if each seems to think that the other is competing for funding, credibility or support.

But Rae does ask a simple question -- "show me the 45-month-old mouse" -- that should be fairly easy to answer.

It's a very good question. I always chalked Rae's anti-resveratrol stance to religion, since he's pretty fanatical about his practice of CR. Still, I too wonder where the 45-month-old mouse is hiding. I'm beginning to think maybe there isn't one. This would bode poorly for Sirtris. It would be churlish of me to accuse them of suppressing such a negative result while the venture guys and Sirtris insiders unload their stock as fast as they can without arousing too much suspicion, so I won't say that. It is after all, perhaps a tad paranoid, and I wouldn't want to accuse venture capitalists or corporate insiders of the sin of greed either. I'm still taking resveratrol, since even if it doesn't extend max lifespan, from the effects I'm aware of, it looks like it could square the curve, and that's ok with me.




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